Newswise — A fresh analysis performed at Tel Aviv University and the Sheba Medical Center unveils how melanoma tumor cells impact their nearby surroundings to aid their requirements - by generating fresh lymph channels in the dermis to penetrate further into the skin and extend throughout the body. The scientists hold the view that this novel finding might aid in the advancement of an immunization against this fatal cancer.
The significant advancement was spearheaded by Prof. Carmit Levy from TAU's Faculty of Medicine and Prof. Shoshana Greenberger of the Sheba Medical Center. The research received funding from ICRF (the Israel Cancer Research Fund) and its findings were published in the Journal of Investigative Dermatology, a publication affiliated with Nature.
Melanoma, the most lethal form of skin cancer, initiates with unregulated proliferation of melanocyte cells in the epidermis, the uppermost layer of the skin. In the subsequent phase, the cancerous cells infiltrate the dermis and disseminate via the lymphatic and circulatory systems. Previous research noted a striking increase in the concentration of lymphatic vessels in the vicinity of melanoma, a phenomenon that had eluded comprehension by scientists until this recent discovery.
"Our central research inquiry focused on understanding the influence of melanoma on lymph vessel formation, which serves as a pathway for its metastasis," elucidates Prof. Greenberger. "We have successfully demonstrated, for the first time, that during the initial phase within the epidermis, melanoma cells secrete extracellular vesicles known as melanosomes. These vesicles possess a notable impact on their surrounding environment. By examining human melanomas sourced from the Pathology Institute, we have established that melanosomes are capable of infiltrating lymph vessels. Furthermore, our investigation of their behavior within the vicinity of lymph vessel cells unveiled their ability to penetrate these cells and stimulate replication and migration. Put simply, the primary melanoma releases extracellular vesicles, specifically melanosomes, that penetrate lymph vessels and promote the development of additional lymph vessels near the tumor. This facilitation enables the melanoma to progress towards the critical metastatic stage, which is often fatal."
Prof. Carmit Levy further contributes, stating, "Prior to melanoma cells reaching the dermis, they secrete extracellular vesicles called melanosomes. These vesicles play a crucial role in altering the dermal environment to create a favorable condition for cancer cells. As a result, melanoma cells actively contribute to enhancing the presence of lymph vessels within the dermis, effectively preparing the groundwork for their own metastasis. Our ongoing studies are currently exploring additional aspects, revealing that the impact of melanosomes extends beyond the lymphatic cells and also affects the immune system, among other areas."
Given that melanoma is not inherently dangerous during the premetastatic stage, gaining a comprehensive understanding of the mechanisms involved in the spread of metastases through the lymphatic and circulatory systems holds promising potential for the development of a vaccine against this highly lethal form of cancer.
"Melanoma that remains confined to the skin poses minimal danger," emphasizes Prof. Greenberger. "As a result, the most encouraging approach in combating melanoma lies in immunotherapy: the development of a vaccine capable of stimulating the immune system to target the melanosomes and, more specifically, to attack the lymphatic endothelial cells that have already been infiltrated by the melanosomes. By halting the mechanisms responsible for metastasis formation in the lymph nodes, we have the potential to impede the progression of the disease and prevent its spread."
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